Directed mutational scanning reveals a balance between acidic and hydrophobic residues in strong human activation domains.

Acidic activation domains are intrinsically disordered regions of the transcription factors that bind coactivators. The intrinsic disorder and low evolutionary conservation of activation domains have made it difficult to identify the sequence features that control activity. To address this problem, we designed thousands of variants in seven acidic activation domains and measured their activities with a high-throughput assay in human cell culture. We found that strong activation domain activity requires a balance between the number of acidic residues and aromatic and leucine residues. These findings motivated a predictor of acidic activation domains that scans the human proteome for clusters of aromatic and leucine residues embedded in regions of high acidity. This predictor identifies known activation domains and accurately predicts previously unidentified ones. Our results support a flexible acidic exposure model of activation domains in which the acidic residues solubilize hydrophobic motifs so that they can interact with coactivators. A record of this paper's transparent peer review process is included in the supplemental information.

Israel rake retractor modification to improve exposure during oropharyngeal surgery on patients with larger body habitus.

PURPOSE: Elective oropharyngeal surgery including tonsillectomy and uvulopalatopharyngoplasty performed for obstructive sleep apnea is increasingly performed on patients of larger body habitus. The use of the Crowe-Davis retractor in such patients may be complicated by a large barrel-chest making it difficult to anchor the retractor to the Mayo stand for suspension limiting oropharyngeal exposure. Here, we present a simple modification using the Israel Retractor to facilitate suspension of the Crowe-Davis mouth gag. METHODS: Operational instructions were followed for Israel retractor modification in oropharyngeal surgery. RESULTS: The Crowe-Davis retractor is able to anchor to the Israel retractor, whose prongs articulate on the Mayo Stand for suspension. This extension allows suspension of patients with larger body habitus in oropharyngeal surgery. CONCLUSIONS: Use of the Israel retractor as an extension of the Crowe-Davis retractor handle provides an easy, quick, safe, and reliable method for placing patients of larger body habitus into suspension.